Stress significantly impacts the structure and function of the brain, particularly the hippocampus, amygdala, and prefrontal cortex (PFC). The hippocampus, initially a focal point for understanding stress and brain plasticity, has revealed how stress affects neuronal structure through mechanisms involving glucocorticoids, excitatory amino acids (EAAs), and epigenetic changes. Chronic stress leads to dendritic retraction and reduced spine density in the hippocampus, while acute stress can enhance memory and excitability. The amygdala also undergoes structural changes, with chronic stress increasing dendritic length in the basolateral amygdala (BLA) and reducing spine density in the medial amygdala. The PFC, crucial for executive functions, shows structural remodeling under stress, with implications for cognitive and emotional regulation. These changes are mediated by complex interactions between stress hormones, neurotransmitters, and signaling pathways, including the role of brain-derived neurotrophic factor (BDNF) and endocannabinoids. Epigenetic mechanisms, such as DNA methylation and histone modifications, play a critical role in stress-induced plasticity and the long-term effects of early-life experiences. Stress also affects mood disorders and aging, with implications for the development of rapid-acting antidepressants and interventions to mitigate stress-related brain damage. Overall, the dynamic interplay between stress, neuroplasticity, and epigenetics underscores the brain's adaptability and vulnerability to environmental challenges.Stress significantly impacts the structure and function of the brain, particularly the hippocampus, amygdala, and prefrontal cortex (PFC). The hippocampus, initially a focal point for understanding stress and brain plasticity, has revealed how stress affects neuronal structure through mechanisms involving glucocorticoids, excitatory amino acids (EAAs), and epigenetic changes. Chronic stress leads to dendritic retraction and reduced spine density in the hippocampus, while acute stress can enhance memory and excitability. The amygdala also undergoes structural changes, with chronic stress increasing dendritic length in the basolateral amygdala (BLA) and reducing spine density in the medial amygdala. The PFC, crucial for executive functions, shows structural remodeling under stress, with implications for cognitive and emotional regulation. These changes are mediated by complex interactions between stress hormones, neurotransmitters, and signaling pathways, including the role of brain-derived neurotrophic factor (BDNF) and endocannabinoids. Epigenetic mechanisms, such as DNA methylation and histone modifications, play a critical role in stress-induced plasticity and the long-term effects of early-life experiences. Stress also affects mood disorders and aging, with implications for the development of rapid-acting antidepressants and interventions to mitigate stress-related brain damage. Overall, the dynamic interplay between stress, neuroplasticity, and epigenetics underscores the brain's adaptability and vulnerability to environmental challenges.